Our aim is to determine the three-dimensional structure of various forms of the thyroid hormone receptor. In the previous year we have succeeded in determining the structure of the ligand-binding domain of the rat thyroid hormone receptor alpha isoform. This structure was a complex with hormone and thus provided the first information about how ligands bind to the large family of steroid/thyroid/retinoid receptors. Our next objectives are to obtain additional structures with different ligands to understand further the mechanisms of ligand binding and the conformation changes associated with binding. We also aim to obtain the structure of the fulllength receptor to understand how the ligand-binding domain works together with the DNA-binding and N-terminal transactivation domains. The Computer Graphics Laboratory has served as an essential resource facility to allow us to view the structures we obtain, to develop models of how the proteins function.